Synthesis and in vitro activity of N-benzyl-1-(2,3-dichlorophenyl)-1H-tetrazol-5-amine P2X7 antagonists
| Autor: | Sridhar Peddi, Diana L. Donnelly-Roberts, Connie R. Faltynek, Arturo Perez-Medrano, Derek W. Nelson, Tongmei Li, Alan S. Florjancic, William A. Carroll, Michael F. Jarvis, Marian T. Namovic |
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| Rok vydání: | 2011 |
| Předmět: |
Purinergic P2X Receptor Antagonists
Stereochemistry Clinical Biochemistry Tetrazoles Pharmaceutical Science Biochemistry Chemical synthesis Sulfone Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Animals Humans Moiety Potency Amines Molecular Biology Molecular Structure Chemistry organic chemicals Organic Chemistry Antagonist In vitro Rats Benzyl group Molecular Medicine Amine gas treating Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:3297-3300 |
| ISSN: | 0960-894X |
| Popis: | Synthesis and biological evaluation of a novel class of substituted N-benzyl-1-(2,3-dichlorophenyl)-1H-tetrazol-5-amine derivatives resulted in the identification of potent P2X7 antagonists. These compounds were assayed for activity at both the human and rat P2X7 receptors. On the benzyl moiety, a variety of functional groups were tolerated, including both electron-withdrawing and electron-donating substituents. Ortho-substitution on the benzyl group provided the greatest potency. The ortho-substituted analogs showed approximately 2.5-fold greater potency at human compared to rat P2X7 receptors. Compounds 12 and 38 displayed hP2X7 pIC50s >7.8 with less than 2-fold difference in potency at the rP2X7. |
| Databáze: | OpenAIRE |
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